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1.
Sci Rep ; 5: 17569, 2015 Dec 02.
Article in English | MEDLINE | ID: mdl-26627131

ABSTRACT

The development of the cornea, a highly specialized transparent tissue located at the anterior of the eye, is coordinated by a variety of molecules and cells. Here, we report that mast cells (MCs), recently found to be involved in morphogenesis, played a potentially important role in corneal development in mice. We show that two different waves of MC migration occurred during corneal development. In the first wave, MCs migrated to the corneal stroma and became distributed throughout the cornea. This wave occurred by embryonic day 12.5, with MCs disappearing from the cornea at the time of eyelid opening. In the second wave, MCs migrated to the corneal limbus and became distributed around limbal blood vessels. The number of MCs in this region gradually increased after birth and peaked at the time of eyelid opening in mice, remaining stable after postnatal day 21. We also show that integrin α4ß7 and CXCR2 were important for the migration of MC precursors to the corneal limbus and that c-Kit-dependent MCs appeared to be involved in the formation of limbal blood vessels and corneal nerve fibers. These data clearly revealed that MCs participate in the development of the murine cornea.


Subject(s)
Cell Movement/physiology , Cornea/embryology , Mast Cells/metabolism , Organogenesis/physiology , Animals , Cornea/blood supply , Mast Cells/cytology , Mice
2.
Int J Mol Sci ; 12(6): 3409-21, 2011.
Article in English | MEDLINE | ID: mdl-21747684

ABSTRACT

OBJECTIVE: To detect the expression and clinical significances of Lewis y antigen and integrin αv, ß3 in epithelial ovarian tumors, and to explore the expression correlation between Lewis y antigen and integrin αv, ß3. METHODS: Immunohistochemical staining was performed in 95 cases of epithelial ovarian cancer, 37 cases of borderline tumors, 20 cases of benign tumors, and 20 cases of normal ovarian tissue, for the detection of Lewis y antigen and integrin αv, ß3 expressions, and to analyze the relationship between Lewis y antigen and integrin, and the relationship between clinical and pathological parameters of ovarian cancer. In addition, immunofluorescence double labeling was utilized to detect the expression correlation between Lewis y antigen and integrin αv, ß3 in ovarian cancer. RESULTS: In epithelial ovarian tumors, the expression rate of Lewis y antigen was 81.05%, significantly higher than that of borderline (51.53%) (P < 0.05) and benign (25%) (P < 0.01) tumors, and normal ovarian tissues (0) (P < 0.01). The expression rate of integrin αv, ß3 in malignant epithelial ovarian tumors was 78.95% and 82.11%, respectively, significantly higher than that of the borderline (45.94%, 40.54%) (both P < 0.05), benign group (10.00%, 15.00%) (both P < 0.01) and normal ovary group (5%, 15%) (both P < 0.01). CONCLUSIONS: Lewis y and integrins αv, ß3 are relevant to pelvic and abdominal diffusion and metastasis of ovarian cancer cells, suggesting that these two molecules mediate a boosting function for tumor metastasis.


Subject(s)
Integrin alphaVbeta3/metabolism , Lewis Blood Group Antigens/metabolism , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Abdominal Neoplasms/metabolism , Abdominal Neoplasms/pathology , Abdominal Neoplasms/secondary , Adult , Aged , Carcinoma, Ovarian Epithelial , Female , Fluorescent Dyes/chemistry , Humans , Immunohistochemistry , Middle Aged , Neoplasm Staging , Neoplasms, Glandular and Epithelial/metabolism , Ovarian Neoplasms/metabolism
3.
Anat Rec (Hoboken) ; 294(6): 961-9, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21542140

ABSTRACT

Lewis (y) antigen, a difucosylated oligosaccharide, has been shown to be associated with malignant properties of ovarian carcinomas. In this study, we have investigated the potential role of Lewis (y) antigen, which was stably transfected into ovarian cancer RMG-1 cells, on carboplatin-induced apoptosis. Overexpression of Lewis (y) antigen effectively protected vitronectin-adherent RMG-1 cells from carboplatin-induced apoptosis as assessed by Hoechst 33258 staining and flow cytometry. Treatment with anti-Lewis (y) antigen, anti-integrin αv, or anti-integrin ß3 antibody partially abolished the protective effect on apoptosis and markedly inhibited the expression of Topo-II ß in cells overexpressing Lewis (y) antigen (all P < 0.01). Moreover, elevated expression of Topo-I and Topo-II ß was found in Lewis (y) antigen-overexpressing cells (P < 0.01). However, no obvious changes in Topo-II α were observed throughout the study (P > 0.05). Taken together, these data suggest that the overexpression of Lewis (y) antigen confers cell adhesion-mediated drug resistance to apoptosis in ovarian cancer cells by the upregulation of Topo-I and Topo-II ß. Therefore, the inhibition of Lewis (y) antigen may be a novel strategy of cancer chemotherapy.


Subject(s)
Apoptosis/physiology , Carboplatin/pharmacology , DNA Topoisomerases, Type II/biosynthesis , DNA Topoisomerases, Type I/biosynthesis , DNA-Binding Proteins/biosynthesis , Lewis Blood Group Antigens/biosynthesis , Ovarian Neoplasms/metabolism , Up-Regulation/physiology , Apoptosis/drug effects , Cell Line, Tumor , DNA Topoisomerases, Type I/genetics , DNA Topoisomerases, Type II/genetics , DNA-Binding Proteins/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Ovarian Neoplasms/prevention & control , Poly-ADP-Ribose Binding Proteins , Up-Regulation/drug effects
4.
Int J Gynecol Cancer ; 20(9): 1482-9, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21119363

ABSTRACT

INTRODUCTION: This study investigates the expression and the clinical significance of Lewis y and integrins α5 and ß1 in serous and mucinous ovarian tumors and then evaluates the association between them. METHODS: Lewis y and integrin α5 and ß1 expression are detected on tissues from malignant, borderline, and benign ovarian serous and mucinous tumors and normal tissues. Their expression and relationship are assessed in paraffin sections using immunohistochemistry and double-labeling immunofluorescence method. RESULTS: Lewis y was mainly expressed in ovarian serous and mucinous cancers (88.33%); its positive rate was obviously higher than rates in the borderline (60.00%, P < 0.05) and benign ovarian tumors (35.00%, P < 0.01) and normal ovarian tissues (0, P < 0.01) and was not associated with clinicopathological characteristics. Integrins α5 (85.00%) and ß1 (81.67%) were also mainly expressed in ovarian serous and mucinous cancers; their positive rates were all obviously higher than those in benign ovarian tumors (60.00% and 55.00%, respectively; all P < 0.05) and normal tissues (40.00% and 30.00%, respectively; all P < 0.01). Increased expression of integrins α5 and ß1 correlated with higher clinical stage (P < 0.05) but were not associated with histological types, differentiation degree, and lymphatic metastasis (P > 0.05). The expression intensity of Lewis y and integrins α5 and ß1 was significant with clinical stage and differentiation degree (all P < 0.05) in ovarian cancer; positive significant correlation between Lewis y antigen and integrins α5 and ß1 was observed in serous and mucinous ovarian cancer tissues. CONCLUSIONS: A close correlation between Lewis y, integrins α5 and ß1, and ovarian cancer was observed. Lewis y can influence the biological behavior of a tumor cell as an important composition of integrins α5 and ß1 by some signal pathway, such as promoting cell adhesion and migration, and this study provides theoretical evidence of ovarian cancer biological treatment.


Subject(s)
Adenocarcinoma, Mucinous/metabolism , Cystadenocarcinoma, Serous/metabolism , Integrin alpha5/metabolism , Integrin beta1/metabolism , Lewis Blood Group Antigens/metabolism , Ovarian Neoplasms/metabolism , Adenocarcinoma, Mucinous/diagnosis , Adenocarcinoma, Mucinous/pathology , Adolescent , Adult , Aged , Biomarkers, Tumor/analysis , Biomarkers, Tumor/metabolism , Case-Control Studies , Cystadenocarcinoma, Serous/diagnosis , Cystadenocarcinoma, Serous/pathology , Female , Humans , Integrin alpha5beta1/metabolism , Middle Aged , Neoplasm Staging/methods , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/pathology , Prognosis , Young Adult
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